Synthesis of ortho-alkyl-p-alkoxyphenols



United States Patent 6 Robert I L; Roseuwald,'Western'Springs,'Ill.,assignor to Universal Oil Products Company, Des Plaincs, IlL, a

corpoiatio'n (if-Delaware I Application December 28, 1953 Serial No.400,818 s Claii'ns, (01260-613) No'Dravuiiig:

This application is a continuation-impart of my co pending applicationSerial-No. 244,464, filed August 30, 1951 now'abandonedl This invention"relates to the synthesis of ortho-alkylp-alkoxyphenols, and moreparticularly to the preparation of ortho tertelkyl p-alkoxyphenols; I

More p'articularly' the present invention is directed to a combinationprocess which comprises the alkylation of hydro'quinon'e' to form amoho-alkyl-hydroquinone and the etherification' ofsaidrhonmalkyl-hydroquinone to form an'ortho-alkyl p-alkoxyphenoliOrtho-alkyl-p-alkoxyphen'ols are generally prepared in low yields by afour-step, process. In thefirst step, hydroquinoneis etherifi'ed,usually in caustic solution, with an etherification agent such asdialkyl sulfate, alkyl halide, etc. This reaction sutiers fromthe'disadv-antage that there is no-knownmca'ns of preventing thereact-ionfrom going too far with the subsequent formation-of largequantities of, 114-dialkoxybehzenes: The desired reaction product,thep-alkoxyphenol, must then be separated from the 1,4-.dialkox'yhenzeneby a suitable means, such as a caustic extraction;V-followed by a neutralization, or by dis'tillation, etc. The extraoperations are, of course, highly 'undesir able. The thusseparated-p-alkoXYpenol is then alkylated by one of thewell-knownmethods such as with an olefin, alcohol, alkyl halide',etc., in thepresence ofa suitable fluoride, etc. The reaction product obtainedtherefrom is a mixture of the desired ortho-alkyl-p-alkoxyphenol alongwith aBQut-"an eq'u'al quantity of-- undesired m-alkylp-allcoxyphenoliThe desired ortho-alkyl p-alkoxyphenol must their be separated from theundesired reaction product, usually by the difference in causticsolubility of the Such'oper'ations are, or" course, highly undesirablelIn accordance with the present invention, hydroquinone, obtained fromanysuitable source, is converted into an orthoaalkyl-p-alltoxyphcnol' intwo steps and with a minimum formation of undesirable by-products.

In accordancewith the present invention, hydroquinone is reacted witlran alkylating agent in the presence ofan alkyl'ating' catalyst. Suitablealkylating agents include a'riolefin, alcohol, alkyl halide, or otherolefinproducing catalyst such as sulfuric acid, phosphoric acid,hydrogen 2,781,404 Patented Feb; 12-, 1957 below'to about 300 C. Theparticular temperature to be employed will depend upon the strength ofthe acid; catalyst-used and in' general itmay be stated that lowertemperatures maybe employed with the stronger acid catalysts Whilehigher temperatures are required with weaker a'cidcatalysts.

In accordance with the present invention, the mono alkyl hydroquinoneproduced as hereinbefore set forth, is reacted with an etheri-fyingagent, usually in the presence of caustic. Suitableetheri-fying agentsinclude d-ialkyl sulfates, alky1 halides, and in some cases alcohols andethe'rs. Thus, if ortho tertbutyl-p-methoxyphenol is desired,mono-tert-butyl hydroquinone may be etherified with dirnethyl sulfate,methyl iodide, methyl bromide, or methylchloride, in the presence-ofcaustic, or with methyl alcohol or diniethyl ether under hightemperature (150- 225 0.), high presure' (100-2000 p; s. i.) conditions.

Other etherifying' agents include vinyl ethers to produce substitutedalkoxy' derivatives. The following reaction with dihydropyran, anexample of a vinyl ether, canbe carried out in the presence of an acidcatalyst:

The etherification reaction may be effected at a suitable temperaturewhich in general will range from room temperature to about 300 C.

In carrying out the etheriiicationreaction, the mo! ratio of alkylhydroquinone reactantgto e-therification a'gent reactant will range fromabout 08 to about 1.25. While equi'molecular quantities of the reactantsare normally utilized,- an excess of ethcrification agent, as indicatedabove, will still-result in high yields of the desiredortho-alkyl-p-allcoxyphenol product.

Both the alkylation reaction and the etherification reaction ashereinbe'for'e set forth may be carried out in the material. Thus; if,teft-butyl hydroquinone is desired,

isobu' "he .or alkyla'tih'g agent.

Any suitable" allylzition catalyst r'n'a-y he used. Partic ularlypreferred alkylatingcatalysts comprise metal hal- V ides such asalumihumc'hlorid"e, Zinc chloride, ferric chloride, etc., naturallyoccurring clays which may or may not be acid activated, such as Tonsil,Filtrol, etc., and synthetically prepared mixtures of silica andnonreduciole metal oxide such as silica-alumina, silica-magnesia,silicazirconia, etc. In some cases acids such as sulfuric acid,

phosphoric acid, hydrofluoric acid, etc, may be employed.

arawt ialcoholymay be used asthe i presence of a suitable solvent. Suchsolvents include saturated'hydrocarbo'ns such as paraflins andcycloparaffins, and mixtures thereof, aromatic hydrocarbons such asbenzene, toluene, xylenes, and mixtures thereof with thebefore-mentioned saturated hydrocarbons, alcohols such as methylalcohol, ethyl alcohol, propyl alcohol, etc, li'e't'o'nes' such asacetone, methyl ethyl ketone, etc, aldehydes; nitroparafiins, water,etc. The actual solvent for use in each reaction will depend uponsolubility factors, temperature ranges in which the reaction is to becarried out, etc. Particularly preferred" solvents cornprise thearomatic hydrocarbons and the aicohols.

In accordance with the present invention, hydroquinone' is convertedinto an ortho-alkyl-p-alkoxyphenol' by a combination of an alkyla-tionreaction followed by an etherification reaction. has the advantage ofaccomplishing thisconversion with a .minirnujm formation of anyundesirable by-products, "thereby eliminating the necessity of furtherpurification steps.

As further examples of typical reactiohs effectedin accordance wasthepresen-t invention, .mono-i-s'op'ro'pyl hydroquinone may beetherified in a methanol solution in the presence of potassium hydroxideto produce orthoisopropyl-p-methoxyphenol. The mono-isopr'cpylhydroquinone may be prepared by reacting hydroquinone with propyleneunder pressure in the presence of a silica.- alumina catalyst. I

Similarly, mono-tert-butyl hydroquinone may be etheritied in a caustictoluene solution with dimethylsultate to produceortho-tert-butyl-p-methoxyphenol; The mono- It is apparent that thisprocess tert-butyl hydroquinone may be prepared by reacting hydroquinonewith tert-butyl chloride in the presence of zinc chloride as a catalyst.

The ortho-alkyl-p-alkoxyphenols formed in accordance with the presentinvention, are useful as antioxidants in organic substances whichdeteriorate due to oxidation, polymerization, or other undesiredreactions. In fact, ortho-alkyl-p-alkoxyphenols are about three times aspotent in antioxidant activity as their meta-alkyl isomers which haveheretofore been formed in approximately equal quantities along with thedesired ortho-alkyl isomers. The ortho-alkyl-p-alkoxyphenols may also beused as germicides, fungicides, etc. Q

The following examples are introduced to illustrate further the noveltyand utility of the present invention but not with the intention ofunduly limiting the same.

Example I Mono-tert-butyl-hydroquinone was prepared by butylation of ahydroquinone as follows. A mixture of hydroquinone (220 grams),silica-alumina catalyst (20 grams), and isobutylene (140 grams) washeated in a rotating three-liter autoclave for seven hours at 200 C.This reaction mixture was extracted with 1 liter of boiling benzene,thus separating the butylated hydroquinone which is soluble therein fromthe unreacted hydroquinone which can then be reused or recycled. Forpurification purposes, the butylated hydroquinone was dissolved in 8%sodium hydroxide solution and then' sprung therefrom by neutralizationwith dilute sulfuric acid. This yielded 105 grams of mono-tert-butylhydroquinone. Crystallization of a portion of this product in methylalcohol gave purified mono-teit-butyl hydroquinone, M. I. 126-128 C.

16.6 grams of the thus produced mono-tert-butyl hydroquinone wasdissolved in 200 m1. of toluene to which 5.9 grams of sodium methylatehad been added. The mixture was heated to 100 C. and 13.9 grams ofdimethyl sulfate were added rapidly with stirring to the hot solution.The stirring was continued for 30 minutes.

The methyl alcohol formed during the reaction was removed bydistillation from the hot toluene solution. After cooling, the reactionmixture Was extracted with Claisen solution (25% KOH, 25% H20, and 50%methyl alcohol) and after neutralization, analyzed by infraredtechniques. The tert-butyl-p-methoxyphenol fraction contained 89%ortho-tert-butyl-p-methoxyphenol and 11%meta-tert-butyl-p-methoxyphenol.

Example II 16.6 grams of mono-tert-butyl hydroquinone as described inExample I was dissolved in 200 ml. of methyl alcohol to which 7.0 gramsof potassium hydroxide had been added. To this mixture was added 17.0grams of methyl iodide and the mixture was allowed to stand for 9 daysat room temperature, followed by evaporation of the methyl alcohol, andan extraction of the product with Claisen solution, and a subsequentneutralization. Analysis of the tert-butyl-p-methoxyphenol fractionshowed that it contained 94% ortho-tert-butyl-p-methoxyphenol and 6% ofmeta-tert-butyl-p-methoxyphenol.

I claim as my invention:

1. The process which comprises reacting an orthoalkyl hydroquinone withfrom about 0.8 to about 1.25 mols of an etherification agent per mol ofortho-alkylhydroquinone at a temperature of from about room temperatureto about 300 C. to form a major proportion of an'ortho-alkybp-alhoxyphenol and a minor proportion of ameta-alkyl-p-alkoxyphenol.

2. The process of claim 1 further characterized in that saidetherification agent is selected from the group consisting ofdimethylsulfate, methyl iodide, methyl bromide, methyl chloride, methylalcohol and .dimethyl ether.

3. The process which comprises reacting an orthotertiary alkylhydroquinone with from about 0.8 to about 1.25 mols of an etherificationagent per mol of orthotertiary alkyl hydroquinone at a temperature offrom about room temperature to about 300C. to form a major proportion ofan ortho-tertiary-alkyl-p-alkoxyphenol and a minor proportion of ameta-tertiary-alkyl p alkoxyphenol.

4. The process which comprises reacting an orthotertiary butylhydroquinone with from about 0.8 to about 1.25 mols of an etherificationagent per mol of orthotertiary butyl hydroquinone at a temperature offrom about room temperature to about 300 C. to form a major proportionof an ortho-tertiary-butyl-p-alkoxyphenol and a minor proportion of ameta-tertiary-butylp-alkoxyphenol.

5. The process which comprises reacting an orthoalkyl hydroquinone withfrom about 0.8t0 about 1.25 mols of an etherification agent per mol ofortho-alkyl hydroquinone, said reaction being carried out in thepresence of caustic at a temperature of from about room temperature toabout 300 C. with an etherification agent selected from the groupconsisting of dimethylsulfate, methyl iodide, methyl bromide, and methylchloride, to form a major proportion of an ortho-alkyl-p-methoxyphenoland a minor proportion of a meta-alkyl-p-methoxyphenol.

6. The process which comprises reacting an orthotertiary alkylhydroquinone with from about 0.8 to about 1.25 mols of an etherificationagent per mol of orthotertiary alkyl hydroquinone, said reaction'beingcarried out in the presence of caustic at a temperature of from aboutroom temperature toabout 300 C. with an etherification agent selectedfrom the group consisting of dimethylsulfate, methyl iodide, methylbromide, and methyl chloride, to form a major proportion of anortho-tertiaryalkyl-p-methoxyphenol and a minor proportion of ametatertiary-alkyl-p-methoxyphenol.

7. The process which comprises reacting an orthotertiary butylhydroquinone with from about 0.8 to about 1.25 mols of an etherificationagent per mol of orthotertiary butyl-hydroquinone, said reaction beingcarried out in the presence of caustic at a temperature of from aboutroom temperature to about 300 C. with an etherification agent selectedfrom the group consisting of dimethylsulfate, methyl iodide, methylbromide, and methyl chloride, to form a major proportion of anortho-tertiarybutyl-p-methoxyphenol and a minor proportion of ametatertiary-butyl-p-methoxyphenol. I

V 8. The process which comprises reacting an orthoalkyl hydroquinonewith from about 0.8 to about 1.25 mols of an etherification agentselected from the group consisting of methyl alcohol and dirnethyl etherper mol of ortho-alkyl hydroquinone at a temperature of from about 150to about 225 C. and a pressure of from about to about'2000 p. s. i. toform a major proportion of an ortho-alkyl-p-methoxyphenol and a minorproportion of a meta-alkyl-p-methoxyphenol.

No references cited.

1. THE PROCESS WHICH COMPRISES REACTING AN ORTHOALKYL HYDROQUINONE WITHFORM ABOUT 0.8 TO ABOUT 1.25 MOLS OF AN ETHERIFICATION AGENT PER MOL OFORTHO-ALKYLHYDROQUINONE AT A TEMPERATURE OF FROM ABOUT ROOM TEMPERATURETO ABOUT 300*C. TO FORM A MAJOR PROPORTION OF ANORTHRO-ALKYL-P-ALKOXYPENOL AND A MINOR PROPORTION OF AMETA-ALKYL-P-ALKOXYPHENOL.